Endocrine Abstracts

Background: Acidosis activates the hypothalamic-pituitary-adrenal (HPA) axis and induces glucocorticoid-mediated atrophy of skeletal muscle. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive cortisone to active cortisol and modulates glucocorticoid signalling locally within skeletal muscle. Here, we address a gap in knowledge how acidosis affects 11β-HSD1 activity in human skeletal muscle cells.Methods: Quadrice...

Background: Chronic kidney disease aggravates loss of skeletal muscles mass and function, which is an independent risk factor for hospitalisation, morbidity and mortality. Glucocorticoid signalling has been implicated as a critical factor in the pathogenesis of muscle atrophy in kidney disease. This study tests whether genetic deletion of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11bHSD1) protects against muscle atrophy in the adenine-die...

Background: Osteoporosis is a common feature of chronic kidney disease (CKD), associated with premature mortality. Glucocorticoids (GCs) are steroid hormones, that in excess, can drive the suppression of bone formation. We have shown that the glucocorticoid (GC) activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is dysregulated in CKD, where it may contribute to the suppression of bone formation. We utilised a murine model of CKD with...

Background: Skeletal muscle wasting is a characteristic feature of chronic kidney disease (CKD), associated with increased hospitalisations and premature mortality. Excess glucocorticoid signalling is a major contributor to the pathogenesis of muscle wasting in conditions of renal impairment. This study aimed to validate a murine model of CKD and utilise this to determine if deletion of 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) provides protec...

11-oxygenated androgens are a group of adrenal-derived C19 steroids that require activation in peripheral tissues. 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) has been shown in vitro to be essential for 11-oxygenated androgen activation, converting 11β-hydroxyandrostenedione (11OHA4) to 11-ketoandrostenedione (11KA4), the direct precursor of the potent androgen 11-ketotestosterone (11KT). As the kidney is the major site of HSD11B2 expression, we hypoth...